Acetaminophen-induced hepatotoxicity is a common consequence of acetaminophen overdose and may lead to acute liver failure (ALF). Currently acetaminophen is the most common cause of ALF in both United States and United Kingdom, with a trend to increasing incidence in the United States. N-acetylcysteine is the most effective drug to prevent progression to liver failure with acetaminophen hepatotoxicity. Liver transplantation is the only definitive therapy that will significantly increase the chances of survival for advanced ALF. This communication reviews current information regarding causes and management of acetaminophen-induced hepatotoxicity and ALF.